In a dual center, randomized, prospective blinded clinical trial, we will investigate how exogenous human surfactant improves the clinical course (as measured by arterial blood cases, mean airway pressures required for therapy, radiographic resolution and frequency of pulmonary sequelae, and death) from the neonatal respiratory distress syndrome in infants of 26-29 weeks gestation. Infants will be treated at birth with human surfactant for prophylactic treatment and infants with established severe respiratory distress syndrome receiving human surfactant for rescue from ventilatory failure will be compared to their respective controls. This study is designed to determine whether surfactant therapy at birth in infants at high risk for RDS modifies the clinical course as determined by FiO2 needed to maintain PaO2 within 50 to 80 torr; mean airway pressures needed for ventilation; changes in the a/A oxygen tension ratio, dynamic compliance, functional residual capacity; frequency of occurrence of pulmonary airleaks; frequency of bronchopulmonary dysplasia; and death within 30 days of birth. This evaluation of the efficacy of human surfactant treatment will determine the extent that surfactant treatment (prophylactic or rescue) modifies the biochemical surfactant profile and surfactant inhibitory activity in serial tracheal aspirates and relate these findings to the clinical severity of RDS. We will evaluate the influence of surfactant therapy on the appearance of left-to-right shunting through the patent ductus arteriosus and its response to indomethacin treatment. We will determine whether surfactant substitution alters biochemical measures of lung injury including pulmonary effluent neutrophilic elastase, Alpha1antiprotease inhibitor levels and activity, and fibronectin, immunologic studies will be performed to determine whether administration of surfactant results in immune reaction injurious to infants treated. Infants in all groups will be enrolled into a neurodevelopmental follow-up program designed to evaluate growth, health history with special emphasis on allergic symptoms and signs, neurologic and developmental performance. This dual centered study will permit a critical analysis of the efficacy, outcome, and adverse effects of human surfactant treatment for severe RDS in very premature infants.